The biotechnology era has experienced significant changes in the number of companies involved in vaccine manufacturing as well as in the production systems they use. Nevertheless, challenges in this area are multiple. In the current vaccine-manufacturing environment, time to market and cost effectiveness are key issues that need to be addressed in addition to smooth R&D and clinical studies. Furthermore, scale up and safety are important for maintaining a successful manufacturing process.

As a result, state-of-the-art technologies to simplify vaccine development and manufacturing are becoming ever-more crucial. In this article, the authors discuss these challenges and evaluate the technologies and process parameters that need to be considered when developing a safe, effective, and economically efficient vaccine. The article primarily deals with prophylactic vaccines.

BACKGROUND

Vaccines are a group of biologics considered to be the lifeline of the human race. It has been said about vaccines that, "With the exception of safe water, no other modality, not even antibiotics, has had such a major effect on mortality reduction..." (1).

A good vaccine is one that elicits an appropriate immune response for the particular pathogen, which could either be a cell-mediated response to tuberculosis or an antibody response to a bacterial or viral infections. It should be safe to use in a variety of patients and the vaccine itself should not cause disease or induce adverse effects. A vaccine should offer long-term protection (ideally lifelong) with one dose and retain its immunogenicity despite adverse storage conditions before administration. Furthermore, it must be inexpensive to make and buy (2).

The development and manufacturing of vaccines must follow four ground rules (3):

Vaccines must be developed, produced, and delivered in large volumes.

Process costs must be kept down.

Development and delivery times must be short.

Patient and employee safety should not be compromised.

The largest market for vaccines is found in the developing world, where doses need to be less expensive than those sold in the developed world in order to have any chance of getting to the patients who need them (4). Companies, therefore, need to weigh the risks of killed or weakened whole organisms against the costs of recombinant vaccine production for products meant to help a large percentage of the economically weak population.

Elements of Biopharmaceutical Production

As part of the "Elements of Biopharmaceutical Production" series (see sidebar), this article presents an overview of the various challenges encountered during process development for the manufacture of prophylactic vaccines.

CHALLENGES

Process development for vaccines can pose unique obstacles for manufacturers. Because most vaccines are new products, there is no history or experience to rely on with regard to how subjects will respond to the drug. Furthermore, promising preclinical results in animal models are generally not duplicated when the therapy is tested in humans. Often, it is challenging to develop robust manufacturing processes and to validate quality control assays for these products because there is a need for a specific biological assay for each product (5).

One important difference between the production of vaccines and other biopharmaceuticals is the risk-safety consideration related to working with pathogens and pathogenic antigens. As with all biomolecules purified from crude biological material, the removal of contaminants (e.g., derivatives from host cell such as DNA, protein, or leachables), must be documented. However, the removal or inactivation of adventitious viruses remains a unique challenge (3).